Pesticide pyrimidinyloxy substituted phenylamidine derivatives

ABSTRACT

The present invention relates to 2,5-disubstituted-4-pyrimidinyl-substituted-phenyl-amidine derivatives of formula (I) in which the substituents are as in the description, notably to 2,5-dialkyl-4-pyrimidinyl-substituted-phenyl-amidine derivatives, their process of preparation, their use as fungicide or insecticide active agents, particularly in the form of fungicide or insecticide compositions, and methods for the control of phytopathogenic fungi or damaging insects, notably of plants, using these compounds or compositions.

The present invention relates to2,5-disubstituted-4-pyrimidinyl-substituted-phenyl-amidine derivatives,notably to 2,5-dialkyl-4-pyrimidinyl-substituted-phenyl-amidinederivatives, their process of preparation, their use as fungicide orinsecticide active agents, particularly in the form of fungicide orinsecticide compositions, and methods for the control of phytopathogenicfungi or damaging insects, notably of plants, using these compounds orcompositions.

In international patent application WO-00/46184 certain phenyl-amidinederivatives are disclosed. However, this document does not specificallydisclose nor suggest to select such compounds wherein the phenyl ring issubstituted according to the invention thus allowing an unexpected andsignificantly higher fungicide or insecticide activity.

It is always of high-interest in agriculture to use novel pesticidecompounds in order to avoid or to control the development of resistantstrains to the active ingredients. It is also of high-interest to usenovel compounds being more active than those already known, with the aimof decreasing the amounts of active compound to be used, whilst at thesame time maintaining an effectiveness at least equivalent to thealready known compounds.

We have now found a new family of compounds which possess the abovementioned effects or advantages.

Accordingly, the present invention provides2,4,5-tris-substituted-phenyl-amidine derivatives of formula (I):

wherein

-   -   R¹ represents H, a substituted or non substituted C₁-C₁₂-alkyl,        a substituted or non substituted C₂-C₁₂-alkenyl, a substituted        or non substituted C₂-C₁₂-alkynyl, SH or a substituted or non        substituted S—C₁-C₁₂-alkyl;    -   R² represents a substituted or non substituted C₁-C₁₂-alkyl;    -   R³ represents a substituted or non substituted C₂-C₁₂-alkyl,        substituted or non substituted C₃-C₆-cycloalkyl, substituted or        non substituted C₂-C₁₂-alkenyl, substituted or non substituted        C₂-C₁₂-alkynyl, halogeno-C₁-C₁₂-alkyl; or    -   R¹ and R², R¹ and R³ or R² and R³ can form together a        substituted or non substituted 5 to 7-membered heterocycle;    -   R⁴ represents a substituted or non substituted C₁-C₁₂-alkyl, a        halogen atom, halogeno-C₁-C₁₂-alkyl, substituted or non        substituted O—C₁-C₁₂-alkyl or cyano;    -   R⁵ represents H, a substituted or non substituted C₁-C₁₂-alkyl,        a halogen atom, halogeno-C₁-C₁₂-alkyl, substituted or non        substituted O—C₁-C₁₂-alkyl or cyano;    -   R⁶ represents H, halogen, CN, substituted or non substituted        phenoxy, substituted or non substituted C₁-C₁₂-alkyl,        halogeno-C₁-C₁₂-alkyl, OR⁷, SR⁷, trialkyl-silyl, COOR⁷,        C(R⁷)═NOR⁷; NR⁷R⁸;    -   R⁷, R⁸ represent independently H, substituted or non substituted        C₁-C₁₂-alkyl, aryl or R⁷ and R⁸ can form a substituted or non        substituted, saturated or non saturated 5 to 7-membered        heterocycle including one or more atoms selected in the list        consisting of O, N and S;    -   m represents 1, 2 or 3;        as well as salts; N-oxydes, metallic complexes, metalloidic        complexes and optically active isomers thereof.

Any of the compounds according to the invention can exist in one or moreoptical or chiral isomer forms depending on the number of asymmetriccentres in the compound. The invention thus relates equally to all theoptical isomers and to their racemic or scalemic mixtures (the term“scalemic” denotes a mixture of enantiomers in different proportions),and to the mixtures of all the possible stereoisomers, in allproportions. The diastereoisomers and/or the optical isomers can beseparated according to the methods which are known perse by the manordinary skilled in the art.

Any of the compounds according to the invention can also exist in one ormore geometric isomer forms depending on the number of double bonds inthe compound. The invention thus relates equally to all geometricisomers and to all possible mixtures, in all proportions. The geometricisomers can be separated according to general methods, which are knownper se by the man ordinary skilled in the art.

For the compounds according to the invention, halogen means either oneof fluorine, bromine, chlorine or iodine and heteroatom can be nitrogen,oxygen or sulphur.

Preferred compounds of formula (I) according to the invention are thosewherein R¹ represents H; C₁-C₁₂-alkyl, preferably C₁-C₁₂-alkyl likemethyl; or SH.

Other preferred compounds of formula (I) according to the invention arethose wherein R² represents methyl.

Still other preferred compounds of formula (I) according to theinvention are those wherein R³ represents C₂-C₁₂-alkyl, preferably a nonsubstituted C₂-C₄-alkyl like ethyl, n-propyl, i-propyl; C₂-C₁₂-alkenyl,preferably C₃-C₄-alkenyl like propenyl or allyl; C₃-C₆-cycloalkyl likecyclopropyl.

Still other preferred compounds of formula (I) according to theinvention are those wherein R² and R³ can form together a substituted ornon substituted 5 to 7-membered heterocycle, preferably a 6-memberedheterocycle, more preferably a pipiridinyl or a pyrrolidinyl, even morepreferably a bis-alkylated-pyrrolidinyl like a bis-methyl-pyrrolidinyl.

Still other preferred compounds of formula (I) according to theinvention are those wherein R⁴ represents a C₁-C₁₂-alkyl, preferably anon substituted C₁-C₁₂-alkyl like methyl; a halogen atom like a chlorineatom.

Still other preferred compounds of formula (I) according to theinvention are those wherein R⁵ represents H, a substituted or nonsubstituted C₁-C₆-alkyl, a halogen atom, halogeno-C₁-C₆-alkyl,substituted or non substituted O—C₁-C₆-alkyl or CN.

Still other preferred compounds of formula (I) according to theinvention are those wherein R⁶ represents H, halogen, CN, substituted ornon substituted phenoxy, substituted or non substituted C₁-C₁₂-alkylnotably branched C₁-C₁₂-alkyl, halogeno-C₁-C₁₂-alkyl, OR⁷, SR⁷,trialkyl-silyl, COOR⁷, C(R⁷)═NOR⁷; NR⁷R⁸ wherein R⁷ and R⁸ are asherein-described.

The above mentioned preferences with regard to the substituents of thecompounds according to the invention can be combined in various manners.These combinations of preferred features thus provide sub-classes ofcompounds according to the invention. Examples of such sub-classes ofpreferred compounds according to the invention can combine:

-   -   preferred features of R¹ with preferred features of R² to R⁶;    -   preferred features of R² with preferred features of R¹ to R⁶;    -   preferred features of R³ with preferred features of R¹ to R⁶;    -   preferred features of R⁴ with preferred features of R¹ to R⁶;    -   preferred features of R⁵ with preferred features of R¹ to R⁶.

In these combinations of preferred features of the substituents of thecompounds according to the invention, the said preferred features canalso be selected among the more preferred features of each of R¹ to R⁶and m so as to form most preferred subclasses of compounds according tothe invention.

The present invention also relates to a process for the preparation ofcompounds of formula (I). Thus according to a further aspect accordingto the invention, there is provided a process P1 for the preparation ofcompound of formula (I) and illustrated according to the followingreaction scheme:

Aminophenylether derivatives of formula (V) can be prepared according toprocess step (a) by reacting aniline derivatives of formula (II)

wherein

-   -   R⁴ and R⁵ are as herein-defined;        with pyrimidine derivatives of formula (III)

wherein

-   -   R⁶ and m are as herein-defined    -   Y represents halogen, triflate, SOMe, mesylate or tosylate;        followed by process step (b) comprising the reduction of        nitrophenylether derivatives of formula (IV) obtained further to        process step (a)

wherein

-   -   R⁴ to R⁶ and m are as herein-defined.

Process step (a) according to the invention can further comprise one ormore of the following characteristics:

-   -   presence of a base;    -   presence of a diluent;    -   presence of a catalyst.

Preferred reaction conditions for carrying out process step (b)according to the invention comprise reaction with stannous chloride inconcentrated hydrochloric acid.

Pyrimidine derivatives of formula (V) can also be prepared according toprocess step (c) by reacting aniline derivatives of formula (VI)

wherein

-   -   R⁴ and R⁵ are as herein-defined;        with pyridine derivatives of formula (III)

wherein

-   -   R⁶ and m are as herein-defined;    -   Y represents halogen, triflate, SOMe, mesylate or tosylate.

Process step (c) according to the invention can further comprise one ormore of the following characteristics:

-   -   presence of a base;    -   presence of a diluent;    -   presence of a catalyst.

Pyrimidine derivatives of formula (V) can also be prepared by knownmethods.

Amidine derivatives of formula (I) can be obtained according to processstep (d) by using aniline derivatives of formula (V) as startingmaterial

wherein

-   -   R⁴ to R⁶ and m are as herein-defined.

Amidine derivatives of formula (I) can be prepared by a further process(d) according to the invention. Various alternatives of process (d)according to the invention can be considered, they are defined asprocess (d1), process (d2) and process (d3) according to the invention.Process (d) according to the invention comprises reacting anilinederivatives of formulae (V) with various reagents thus definingprocesses (d1), (d2) and (d3) respectively. Process (d1) is carried outfurther using amino-acetal derivatives of formula (VII)

wherein

-   -   R¹, R², R³ are as herein-defined;    -   B¹ and B² represent each alkyl or together cycloalkyl.

Process (d1) according to the invention can further comprise one or moreof the following characteristics:

-   -   presence of a acid or base;    -   presence of a diluent.

Process (d2) is carried out further using amine derivatives of formula(VIII)

wherein

-   -   R² and R³ are as herein-defined;        in the presence of orthoester derivatives of formula (IX)

wherein

-   -   R¹ is as herein-defined;    -   B¹, B² and B³ represent each alkyl.

Formula (V) provides a general definition of the aniline derivativesuseful as starting materials for carrying out process (d2) according tothe invention. In this formula R¹, R², R³, R⁴, R⁵, R⁶ and m preferablyrepresent substituents or values as herein-defined in connection withthe description of compounds of formula (I) according to the invention.

Process (d3) is carried out further using amide derivatives of formula(X)

wherein

-   -   R¹, R², R³ are as herein-defined.

Process (d3) according to the invention can further comprise one or moreof the following characteristics:

-   -   presence of a halogenation agent, like PCl₅, PCl₃, POCl₃, SOCl₂;    -   presence of a diluent.

Processes (d), (d1), (d2) or (d3) according to the invention can furthercomprise one or more of the following characteristics:

-   -   presence of an acid or a base;    -   presence of a diluent.

Suitable diluents for carrying out the processes (a), (b) and (c)according to the invention are all customary inert organic solvents.Preference is given to using aliphatic, alicyclic or aromatichydrocarbons, such as petroleum ether, hexane, heptane, cyclohexane,methylcyclohexane, benzene, toluene, xylene or decalin; halogenatedhydrocarbons, such as chlorobenzene, dichlorobenzene, dichloromethane,chloroform, carbon tetrachloride, dichloroethane or trichloro-ethane;ethers, such as diethyl ether, diisopropyl ether, methyl tert-butylether, methyl tert-amyl ether, dioxane, tetrahydrofuran,1,2-dimethoxyethane, 1,2-diethoxyethane or anisole; nitriles, such asacetonitrile, propionitrile, n- or iso-butyronitrile or benzonitrile;amides, such as N,N-dimethylformamide, N,N-dimethylacetamide,N-methylformanilide, N-methylpyrrolidone or hexamethylphosphorictriamide; mixtures thereof with water or pure water.

Suitable diluents for carrying out the processes (d1), (d2) and (d3)according to the invention are in each case all customary inert organicsolvents. Preference is given to using aliphatic, alicyclic or aromatichydrocarbons, such as petroleum ether, hexane, heptane, cyclohexane,methylcyclohexane, benzene, toluene, xylene or decalin; ethers, such asdiethyl ether, diisopropyl ether, methyl tert-butyl ether, methyltert-amyl ether, dioxane, tetrahydrofuran, 1,2-dimethoxyethane,1,2-diethoxyethane or anisole; nitriles, such as acetonitrile,propionitrile, n- or iso-butyronitrile or benzonitrile; amides, such asN,N-dimethylformamide, N,N-dimethyl-acetamide, N-methylformanilide,N-methylpyrrolidone or hexamethylphosphoric triamide; esters, such asmethyl acetate or ethyl acetate; sulphoxides, such asdimethylsulphoxide; or sulphones, such as sulpholane; alcohols, such asmethanol, ethanol, n- or iso-propanol, n-, iso-, sec- or tert-butanol,ethanediol, propane-1,2-diol, ethoxyethanol, methoxyethanol,diethylene-glycolmonomethylether, diethyleneglycolmonoethylether;mixtures thereof with water or pure water.

Suitable acid binders for carrying out the processes (a), (b) and (c)according to the invention are all inorganic and organic bases customaryfor such reactions. Preference is given to using alkaline earth metal oralkali metal hydrides, hydroxides, amides, alcoholates, acetates,carbonates or hydrogen carbonates, such as sodium hydride, sodium amide,lithium diisoproylamide, sodium methanolate, sodium ethanolate,potassium tert-butanolate, sodium acetate, potassium acetate, calciumacetate, sodium hydroxide, potassium hydroxide, sodium carbonate,potassium carbonate, potassium bicarbonate, sodium bicarbonate, orammonium carbonate; and also tertiary amines, such as trimethylamine,triethylamine, tributylamine, N,N-dimethylaniline,N,N-dimethyl-benzylamine pyridine, N-methylpiperidine,N-methylmorpholine, N,N-dimethylaminopyridine, diazabicyclooctane(DABCO), diazabicyclononene (DBN) or di-aza-bicycloundecene (DBU).

Suitable acid binders for carrying out the processes (b), (c), (d)according to the invention are in each case all inorganic and organicbases customary for such reactions. Preference is given to usingalkaline earth metal or alkali metal hydrides, hydroxides, amides,alcoholates, acetates, fluorides, phosphates, carbonates or hydrogencarbonates, such as sodium hydride, sodium-amide, lithiumdiisopropylamide, sodium methanolate, sodium ethanolate, potassiumtert-butanolate, sodium hydroxide, potassium hydroxide, sodium acetate,sodium phosphate, potas-sium phosphate, potassium fluoride, caesiumfluoride, sodium carbonate, potassium carbonate, potassiumhydrogencarbonate, sodium hydrogencarbonate or caesium carbonate; andalso tertiary amines, such as trimethylamine, triethylamine,tributylamine, N,N-dimethylaniline, N,N-dimethyl-benzylamine, pyridine,N-methylpiperidine, N-methylmorpholine, N,N-dimethylamino-pyridine,diazabicyclooctane (DABCO), diazabicyclononene (DBN) ordiazabicycloundecene (DBU).

Suitable acids for carrying out the process (d3) according to theinvention are all inorganic and organic acids customary for suchreactions. Preference is given to using para-toluene sulfonic acid,methane sulfonic acid, hydrochloric acid (gas, aqueous or organicsolution) or sulphuric acid.

Suitable condensing agents for carrying out the process (d1) accordingto the invention are all condensing agents customary for such amidationreactions. Preference is given to using acid halide former, such asphosgene, phosphorous tribromide, phosphorous trichloride, phosphorouspentachloride, phosphorous trichloride oxide or thionyl chloride;anhydride former, such as ethyl chloroformate, methyl chloroformate,isopropyl chloroformate, isobutyl chloroformate or methanesulfonylchloride; carbodiimides, such as N,N′-dicyclo-hexylcarbodiimide (DCC) orother customary condensing agents, such as phosphorous pentoxide,polyphosphoric acid, N,N′-carbonyldiimidazole,2-ethoxy-N-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ),triphenylphosphine/tetrachloromethane orbromo-tripyrrolidino-phosphonium-hexafluorophosphate.

Processes (a), (b) and (c) to the invention can be carried out in thepresence of a catalyst. Preference is given to palladium salts orcomplexes, such as palladium chloride, palladium acetate,tetrakis-(triphenylphosphine) palladium, bis-(triphenylphosphine)palladium dichloride or1,1′-Bis(diphenylphosphino)ferrocenepalladium(II) chloride.

It is also possible to generate a palladium complex directly in thereaction mixture by separately adding to the reaction mixture apalladium salt and a complex ligand, such as triethylphos-phane,tri-tert-butylphosphane, tricyclohexylphosphane,2-(dicyclohexylphosphane)biphenyl, 2-(di-tert-butylphosphan)biphenyl,2-(dicyclohexylphosphane)-2′-(N,N-dimethylamino)-biphenyl,triphenylphosphane, tris-(o-tolyl)phosphane, sodium3-(diphenylphosphino)benzolsulfonate, tris-2-(methoxyphenyl)phosphane,2,2′-bis-(diphenylphosphane)-1,1′-binaphthyl,1,4-bis-(diphenylphosphane)butane, 1,2-bis-(diphenylphosphane)ethane,1,4-bis-(dicyclohexylphosphane)butane,1,2-bis-(dicyclohexylphosphane)ethane,2-(dicyclohexylphosphane)-2′-(N,N-dimethylamino)-biphenyl,bis(diphenylphosphino)ferrocene ortris-(2,4-tert-butylphenyl)-phosphite.

When carrying out processes (d) according to the invention, the reactiontemperature can be varied within a relatively wide range. In general,the process is carried out at temperatures between from 0° C. to 150°C., preferably from 0° C. to 120° C., particularly preferably from 10°C. to 90° C.

When carrying out processes (a), (b), and according to the invention,the reaction temperatures can in each case be varied within a relativelywide range. In general, the processes are carried out at temperaturesfrom 0° C. to 180° C., preferably from 10° C. to 150° C., particularlypreferably from 20° C. to 120° C.

Generally, for carrying out process (a) according to the invention, from0.8 to 15 mole, preferably from 0.8 to 8 mole, of phenol derivative offormula (III) and from 1 to 3 mole of acid binder are employed per moleof pyrimidine derivative of formula (II).

However, it is also possible to employ the reaction components in otherratios.

Work-up is carried out by customary methods.

Water can be added to the reaction mixture and the organic phase can beseparated off and, after drying, concentrated under reduced pressure.The residue that remains may, if appropriate, be freed of any impuritiesthat may still be present using customary methods, such aschromatography or recrystallization.

Processes according to the invention are generally carried out underatmospheric pressure. However, in each case it is also possible tooperate under elevated or reduced pressure—in general from 0.1 bar to 10bar.

Compounds of formula (I) according to the invention can be preparedaccording to the herein described processes. It will nevertheless beunderstood that, on the basis of his general knowledge and of availablepublications, the skilled worker will be able to adapt these processesaccording to the specifics of each of the compounds which it is desiredto synthesise.

In a further aspect, the present invention also relates to a fungicideor insecticide composition comprising an effective and non-phytotoxicamount of an active compound of formula (I).

The expression “effective and non-phytotoxic amount” means an amount ofcomposition according to the invention which is sufficient to control ordestroy the fungi present or liable to appear on the crops, and whichdoes not entail any appreciable symptom of phytotoxicity for the saidcrops. Such an amount can vary within a wide range depending on thefungus to be controlled, the type of crop, the climatic conditions andthe compounds included in the fungicide composition according to theinvention.

This amount can be determined by systematic field trials, which arewithin the capabilities of a person skilled in the art.

Thus, according to the invention, there is provided a fungicide orinsecticide composition comprising, as an active ingredient, aneffective amount of a compound of formula (I) as herein-defined and anagriculturally acceptable support, carrier or filler.

According to the invention, the term “support” denotes a natural orsynthetic, organic or inorganic compound with which the active compoundof formula (I) is combined or associated to make it easier to apply,notably to the parts of the plant. This support is thus generally inertand should be agriculturally acceptable. The support may be a solid or aliquid. Examples of suitable supports include clays, natural orsynthetic silicates, silica, resins, waxes, solid fertilisers, water,alcohols, in particular butanol, organic solvents, mineral and plantoils and derivatives thereof. Mixtures of such supports may also beused.

The composition according to the invention may also comprise additionalcomponents. In particular, the composition may further comprise asurfactant. The surfactant can be an emulsifier, a dispersing agent or awetting agent of ionic or non-ionic type or a mixture of suchsurfactants. Mention may be made, for example, of polyacrylic acidsalts, lignosulphonic acid salts, phenolsulphonic ornaphthalenesulphonic acid salts, polycondensates of ethylene oxide withfatty alcohols or with fatty acids or with fatty amines, substitutedphenols (in particular alkylphenols or arylphenols), salts ofsulphosuccinic acid esters, taurine derivatives (in particular alkyltaurates), phosphoric esters of polyoxyethylated alcohols or phenols,fatty acid esters of polyols, and derivatives of the present compoundscontaining sulphate, sulphonate and phosphate functions. The presence ofat least one surfactant is generally essential when the active compoundand/or the inert support are water-insoluble and when the vector agentfor the application is water. Preferably, surfactant content may becomprised from 5% to 40% by weight of the composition.

Optionally, additional components may also be included, e.g. protectivecolloids, adhesives, thickeners, thixotropic agents, penetration agents,stabilisers, sequestering agents. More generally, the active compoundscan be combined with any solid or liquid additive, which complies withthe usual formulation techniques.

In general, the composition according to the invention may contain from0.05 to 99% by weight of active compound, preferably 10 to 70% byweight.

Compositions according to the invention can be used in various formssuch as aerosol dispenser, bait (ready for use), bait concentrate, blockbait, capsule suspension, cold fogging concentrate, dustable powder,emulsifiable concentrate, emulsion oil in water, emulsion water in oil,encapsulated granule, fine granule, flowable concentrate for seedtreatment, gas (under pressure), gas generating product, grain bait,granular bait, granule, hot fogging concentrate, macrogranule,microgranule, oil dispersible powder, oil miscible flowable concentrate,oil miscible liquid, paste, plant rodlet, plate bait, powder for dryseed treatment, scrap bait, seed coated with a pesticide, smoke candle,smoke cartridge, smoke generator, smoke pellet, smoke rodlet, smoketablet, smoke tin, soluble concentrate, soluble powder, solution forseed treatment, suspension concentrate (=flowable concentrate), trackingpowder, ultra low volume (ulv) liquid, ultra low volume (ulv)suspension, vapour releasing product, water dispersible granules ortablets, water dispersible powder for slurry treatment, water solublegranules or tablets, water soluble powder for seed treatment andwettable powder.

These compositions include not only compositions which are ready to beapplied to the plant or seed to be treated by means of a suitabledevice, such as a spraying or dusting device, but also concentratedcommercial compositions which must be diluted before application to thecrop.

The compounds according to the invention can also be mixed with one ormore insecticide, fungicide, bactericide, attractant, acaricide orpheromone active substance or other compounds with biological activity.The mixtures thus obtained have a broadened spectrum of activity.

The mixtures with other fungicide compounds are particularlyadvantageous. Examples of suitable fungicide mixing partners may beselected in the following lists:

-   -   B1) a compound capable to inhibit the nucleic acid synthesis        like benalaxyl, benalaxyl-M, bupirimate, chiralaxyl, clozylacon,        dimethirimol, ethirimol, furalaxyl, hymexazol, metalaxyl,        metalaxyl-M, ofurace, oxadixyl, oxolinic acid;    -   B2) a compound capable to inhibit the mitosis and cell division        like benomyl, carbendazim, diethofencarb, fuberidazole,        pencycuron, thiabendazole thiophanate-methyl, zoxamide;    -   B3) a compound capable to inhibit the respiration for example    -   as CI-respiration inhibitor like diflumetorim;    -   as CII-respiration inhibitor like boscalid, carboxin, fenfuram,        flutolanil, furametpyr, mepronil, oxycarboxine, penthiopyrad,        thifluzamide;    -   as CIII-respiration inhibitor like azoxystrobin, cyazofamid,        dimoxystrobin, enestrobin, famoxadone, fenamidone,        fluoxastrobin, kresoxim-methyl, metominostrobin, orysastrobin,        pyraclostrobin, picoxystrobin, trifloxystrobin;    -   B4) a compound capable of to act as an uncoupler like dinocap,        fluazinam;    -   B5) a compound capable to inhibit ATP production like fentin        acetate, fentin chloride, fentin hydroxide, silthiofam;    -   B6) a compound capable to inhibit AA and protein biosynthesis        like andoprim, blasticidin-S, cyprodinil, kasugamycin,        kasugamycin hydrochloride hydrate, mepanipyrim, pyrimethanil;    -   B7) a compound capable to inhibit the signal transduction like        fenpiclonil, fludioxonil, quinoxyfen;    -   B8) a compound capable to inhibit lipid and membrane synthesis        like chlozolinate, iprodione, procymidone, vinclozolin,        pyrazophos, edifenphos, iprobenfos (IBP), isoprothiolane,        tolclofos-methyl, biphenyl, iodocarb, propamocarb,        propamocarb-hydrochloride;    -   B9) a compound capable to inhibit ergosterol biosynthesis like        fenhexamid, azaconazole, bitertanol, bromuconazole,        cyproconazole, diclobutrazole, difenoconazole, diniconazole,        diniconazole-M, epoxiconazole, etaconazole, fenbuconazole,        fluquinconazole, flusilazole, flutriafol, furconazole,        furconazole-cis, hexaconazole, imibenconazole, ipconazole,        metconazole, myclobutanil, paclobutrazol, penconazole,        propiconazole, prothioconazole, simeconazole, tebuconazole,        tetraconazole, triadimefon, triadimenol, triticonazole,        uniconazole, voriconazole, imazalil, imazalil sulfate,        oxpoconazole, fenarimol, flurprimidol, nuarimol, pyrifenox,        triforine, pefurazoate, prochloraz, triflumizole, viniconazole,        aldimorph, dodemorph, dodemorph acetate, fenpropimorph,        tridemorph, fenpropidin, spiroxamine, naftifine, pyributicarb,        terbinafine;    -   B10) a compound capable to inhibit cell wall synthesis like        benthiavalicarb, bialaphos, dimethomorph, flumorph,        iprovalicarb, polyoxins, polyoxorim, validamycin A;    -   B11) a compound capable to inhibit melanine biosynthesis like        carpropamid, diclocymet, fenoxanil, phtalide, pyroquilon,        tricyclazole;    -   B12) a compound capable to induce a host defence like        acibenzolar-S-methyl, probenazole, tiadinil;    -   B13) a compound capable to have a multisite action like        captafol, captan, chlorothalonil, copper preparations such as        copper hydroxide, copper naphthenate, copper oxychloride, copper        sulphate, copper oxide, oxine-copper and Bordeaux mixture,        dichlofluanid, dithianon, dodine, dodine free base, ferbam,        fluorofolpet, folpet, guazatine, guazatine acetate,        iminoctadine, iminoctadine albesilate, iminoctadine triacetate,        mancopper, mancozeb, maneb, metiram, metiram zinc, propineb,        sulphur and sulphur preparations including calcium polysulphide,        thiram, tolylfluanid, zineb, ziram    -   B14) a compound selected in the following list: amibromdole,        benthiazole, bethoxazin, capsimycin, carvone, chinomethionat,        chloropicrin, cufraneb, cyflufenamid, cymoxanil, dazomet,        debacarb, diclomezine, dichlorophen, dicloran, difenzoquat,        difenzoquat methylsulphate, diphenylamine, ethaboxam, ferimzone,        flumetover, flusulfamide, fosetyl-aluminium, fosetyl-calcium,        fosetyl-sodium, fluopicolide, fluoroimide, hexachlorobenzene,        8-hydroxyquinoline sulfate, irumamycin, methasulphocarb,        metrafenone, methyl isothiocyanate, mildiomycin, natamycin,        nickel dimethyldithiocarbamate, nitrothal-isopropyl,        octhilinone, oxamocarb, oxyfenthiin, pentachlorophenol and        salts, 2-phenylphenol and salts, phosphorous acid and its salts,        piperalin, propanosine-sodium, proquinazid, pyrroinitrine,        quintozene, tecloftalam, tecnazene, triazoxide, trichiamide,        zarilamid and 2,3,5,6-tetrachloro-4-(methylsulfonyl)-pyridine,        N-(4-chloro-2-nitrophenyl)-N-ethyl-4-methyl-benzenesulfonamide,        2-amino-4-methyl-N-phenyl-5-thiazolecarboxamide,        2-chloro-N-(2,3-dihydro-1,1,3-trimethyl-1H-inden-4-yl)-3-pyridincarboxamide,        3-[5-(4-chlorophenyl)-2,3-dimethylisoxazolidin-3-yl]pyridine,        cis-1-(4-chlorophenyl)-2-(1H-1,2,4-triazole-1-yl)-cycloheptanol,        methyl        1-(2,3-dihydro-2,2-dimethyl-1H-inden-1-yl)-1H-imidazole-5-carboxylate,        3,4,5-trichloro-2,6-pyridinedicarbonitrile, Methyl        2-[[[cyclopropyl[(4-methoxyphenyl)imino]methyl]thio]methyl]-.alpha.-(methoxymethylene)-benzeneacetate,        4-chloro-alpha-propynyloxy-N-[2-[3-methoxy-4-(2-propynyloxy)phenyl]ethyl]-benzeneacetamide,        (2S)—N-[2-[4-[[3-(4-chlorophenyl)-2-propynyl]oxy]-3-methoxyphenyl]ethyl]-3-methyl-2-[(methylsulfonyl)amino]-butanamide,        5-chloro-7-(4-methylpiperidin-1-yl)-6-(2,4,6-trifluorophenyl)[1,2,4]triazolo[1,5-a]pyrimidine,        5-chloro-6-(2,4,6-trifluorophenyl)-N-[(1R)-1,2,2-trimethylpropyl][1,2,4]triazolo[1,5-a]pyrimidin-7-amine,        5-chloro-N-[(1R)-1,2-dimethylpropyl]-6-(2,4,6-trifluorophenyl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine,        N-[1-(5-bromo-3-chloropyridin-2-yl)ethyl]-2,4-dichloronicotinamide,        N-(5-bromo-3-chloropyridin-2-yl)methyl-2,4-dichloronicotinamide,        2-butoxy-6-iodo-3-propyl-benzopyranon-4-one,        N-{(Z)-[(cyclopropylmethoxy)imino][6-(difluoromethoxy)-2,3-difluorophenyl]methyl}2-phenylacetamide,        N-(3-ethyl-3,5,5-trimethyl-cyclohexyl)-3-formylamino-2-hydroxy-benzamide,        2-[[[[1-[3(1        Fluoro-2-phenylethyl)oxy]phenyl]ethylidene]amino]oxy]methyl]-alpha-(methoxyimino)-N-methyl-alphaE-benzeneacetamide,        N-{2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]ethyl}-2-(trifluoromethyl)benzamide,        N-(3′,4′-dichloro-5-fluorobiphenyl-2-yl)-3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxamide,        2-(2-{[6-(3-chloro-2-methylphenoxy)-5-fluoropyrimidin-4-yl]oxy}phenyl)-2-(methoxyimino)-N-methylacetamide,        1-[(4-methoxyphenoxy)methyl]-2,2-dimethylpropyl-1H-imidazole-1-carboxylic        acid,        O-[1-[(4-methoxyphenoxy)methyl]-2,2-dimethylpropyl]-1H-imidazole-1-carbothioic        acid.

The composition according to the invention comprising a mixture of acompound of formula (I) with a bactericide compound may also beparticularly advantageous. Examples of suitable bactericide mixingpartners may be selected in the following list: bronopol, dichlorophen,nitrapyrin, nickel dimethyldithiocarbamate, kasugamycin, octhilinone,furancarboxylic acid, oxytetracycline, probenazole, streptomycin,tecloftalam, copper sulphate and other copper preparations.

The compound of formula (I) and the fungicide composition according tothe invention can be used to curatively or preventively control thephytopathogenic fungi of plants or crops. Thus, according to a furtheraspect of the invention, there is provided a method for curatively orpreventively controlling the phytopathogenic fungi of plants or cropscharacterised in that a compound of formula (I) or a fungicidecomposition according to the invention is applied to the seed, the plantor to the fruit of the plant or to the soil wherein the plant is growingor wherein it is desired to grow.

In the same manner, the compound of formula (I) and the insecticidecomposition according to the invention can be used to curatively orpreventively control damaging insects, notably of plants or crops. Thus,according to a further aspect of the invention, there is provided amethod for curatively or preventively controlling damaging insects,notably of plants or crops, characterised in that a compound of formula(I) or an insecticide composition according to the invention is appliedto the seed, the plant or to the fruit of the plant or to the soilwherein the plant is growing or wherein it is desired to grow.

The method of treatment according to the invention may also be useful totreat propagation material such as tubers or rhizomes, but also seeds,seedlings or seedlings pricking out and plants or plants pricking out.This method of treatment can also be useful to treat roots. The methodof treatment according to the invention can also be useful to treat theoverground parts of the plant such as trunks, stems or stalks, leaves,flowers and fruit of the concerned plant. Among the plants that can beprotected by the method according to the invention, mention may be madeof cotton; flax; vine; fruit or vegetable crops such as Rosaceae sp.(for instance pip fruit such as apples and pears, but also stone fruitsuch as apricots, almonds and peaches), Ribesioidae sp., Juglandaceaesp., Betulaceae sp., Anacardiaceae sp., Fagaceae sp., Moraceae sp.,Oleaceae sp., Actimidaceae sp., Lauraceae sp., Musaceae sp. (forinstance banana trees and plantins), Rubiaceae sp., Theaceae sp.,Sterculiceae sp., Rutaceae sp. (for instance lemons, oranges andgrapefruit); Solanaceae sp. (for instance tomatoes), Liliaceae sp.,Asteraceae sp. (for instance lettuces), Umbelliferae sp., Cruciferaesp., Chenopodiaceae sp., Cucurbitaceae sp., Papilionaceae sp. (forinstance peas), Rosaceae sp. (for instance strawberries); major cropssuch as Graminae sp. (for instance maize, lawn or cereals such as wheat,rice, barley and triticale), Asteraceae sp. (for instance sunflower),Cruciferae sp. (for instance colza), Fabacae sp. (for instance peanuts),Papilionaceae sp. (for instance soybean), Solanaceae sp. (for instancepotatoes), Chenopodiaceae sp. (for instance beetroots) horticultural andforest crops; as well as genetically modified homologues of these crops.

Among the diseases of plants or crops that can be controlled by themethod according to the invention, mention may be made of:

Powdery mildew diseases such as:

-   -   Blumeria diseases, caused for example by Blumeria graminis;    -   Podosphaera diseases, caused for example by Podosphaera        leucotricha;    -   Sphaerotheca diseases, caused for example by Sphaerotheca        fuliginea;    -   Uncinula diseases, caused for example by Uncinula necator;

Rust diseases such as:

-   -   Gymnosporangium diseases, caused for example by Gymnosporangium        sabinae;    -   Hemileia diseases, caused for example by Hemileia vastatrix;    -   Phakopsora diseases, caused for example by Phakopsora pachyrhizi        or Phakopsora meibomiae;    -   Puccinia diseases, caused for example by Puccinia recondita;    -   Uromyces diseases, caused for example by Uromyces        appendiculatus;

Oomycete diseases such as:

-   -   Bremia diseases, caused for example by Bremia lactucae;    -   Peronospora diseases, caused for example by Peronospora pisi        or P. brassicae;    -   Phytophthora diseases, caused for example by Phytophthora        infestans;    -   Plasmopara diseases, caused for example by Plasmopara viticola;    -   Pseudoperonospora diseases, caused for example by        Pseudoperonospora humuli or Pseudoperonospora cubensis;    -   Pythium diseases, caused for example by Pythium ultimum;

Leafspot, leaf blotch and leaf blight diseases such as:

-   -   Alternaria diseases, caused for example by Alternaria solani;    -   Cercospora diseases, caused for example by Cercospora beticola;    -   Cladiosporum diseases, caused for example by Cladiosporum        cucumerinum;    -   Cochliobolus diseases, caused for example by Cochliobolus        sativus;    -   Colletotrichum diseases, caused for example by Colletotrichum        lindemuthanium;    -   Cycloconium diseases, caused for example by Cycloconium        oleaginum;    -   Diaporthe diseases, caused for example by Diaporthe citri;    -   Elsinoe diseases, caused for example by Elsinoe fawcettii;    -   Gloeosporium diseases, caused for example by Gloeosporium        laeticolor;    -   Glomerella diseases, caused for example by Glomerella cingulata;    -   Guignardia diseases, caused for example by Guignardia bidwelli;    -   Leptosphaeria diseases, caused for example by Leptosphaeria        maculans; Leptosphaeria nodorum;    -   Magnaporthe diseases, caused for example by Magnaporthe grisea;    -   Mycosphaerella diseases, caused for example by Mycosphaerella        graminicola Mycosphaerella arachidicola; Mycosphaerella        fijiensis;    -   Phaeosphaeria diseases, caused for example by Phaeosphaeria        nodorum;    -   Pyrenophora diseases, caused for example by Pyrenophora teres;    -   Ramularia diseases, caused for example by Ramularia collo-cygni;    -   Rhynchosporium diseases, caused for example by Rhynchosporium        secalis;    -   Septoria diseases, caused for example by Septoria apii or        Septoria lycopercisi;    -   Typhula diseases, caused for example by Typhula incamata;    -   Venturia diseases, caused for example by Venturia inaequalis;

Root and stem diseases such as:

-   -   Corticium diseases, caused for example by Corticium graminearum;    -   Fusarium diseases, caused for example by Fusarium oxysporum;    -   Gaeumannomyces diseases, caused for example by Gaeumannomyces        graminis;    -   Rhizoctonia diseases, caused for example by Rhizoctonia solani;    -   Tapesia diseases, caused for example by Tapesia acuformis;    -   Thielaviopsis diseases, caused for example by Thielaviopsis        basicola;

Ear and panicle diseases such as:

-   -   Alternaria diseases, caused for example by Alternaria spp.    -   Aspergillus diseases, caused for example by Aspergillus flavus;    -   Cladosporium diseases, caused for example by Cladosporium spp.    -   Claviceps diseases, caused for example by Claviceps purpurea;    -   Fusarium diseases, caused for example by Fusarium culmorum;    -   Gibberella diseases, caused for example by Gibberella zeae;    -   Monographella diseases, caused for example by Monographella        nivalis;

Smut and bunt diseases such as:

-   -   Sphacelotheca diseases, caused for example by Sphacelotheca        reiliana;    -   Tilletia diseases, caused for example by Tilletia caries;    -   Urocystis diseases, caused for example by Urocystis occulta;    -   Ustilago diseases, caused for example by Ustilago nuda;

Fruit rot and mould diseases such as:

-   -   Aspergillus diseases, caused for example by Aspergillus flavus;    -   Botrytis diseases, caused for example by Botrytis cinerea;    -   Penicillium diseases, caused for example by Penicillium        expansum;    -   Sclerotinia diseases, caused for example by Sclerotinia        sclerotiorum;    -   Verticilium diseases, caused for example by Verticilium        alboatrum;

Seed and soilborne decay, mould, wilt, rot and damping-off diseases:

-   -   Fusarium diseases, caused for example by Fusarium culmorum;    -   Phytophthora diseases, caused for example by Phytophthora        cactorum;    -   Pythium diseases, caused for example by Pythium ultimum;    -   Rhizoctonia diseases, caused for example by Rhizoctonia solani;    -   Sclerotium diseases, caused for example by Sclerotium rolfsii;    -   Microdochium diseases, caused for example by Microdochium        nivale;

Canker, broom and dieback diseases such as:

-   -   Nectria diseases, caused for example by Nectria galligena;

Blight diseases such as:

-   -   Monilinia diseases, caused for example by Monilinia laxa;

Leaf blister or leaf curl diseases such as:

-   -   Taphrina diseases, caused for example by Taphrina deformans;

Decline diseases of wooden plants such as:

-   -   Esca diseases, caused for example by Phaemoniella clamydospora;    -   Eutypa dyeback, caused for example by Eutypa lata;    -   Dutch elm disease, caused for example by Ceratocystsc ulmi;

Diseases of flowers and Seeds such as:

-   -   Botrytis diseases, caused for example by Botrytis cinerea;

Diseases of tubers such as:

-   -   Rhizoctonia diseases, caused for example by Rhizoctonia solani.

The fungicide or insecticide composition according to the invention mayalso be used against fungal diseases or damaging insects liable to growor attack on or inside timber. The term “timber” means all types ofspecies of wood, and all types of working of this wood intended forconstruction, for example solid wood, high-density wood, laminated wood,and plywood. The method for treating timber according to the inventionmainly consists in contacting one or more compounds according to theinvention, or a composition according to the invention; this includesfor example direct application, spraying, dipping, injection or anyother suitable means. The dose of active compound usually applied in themethod of treatment according to the invention is generally andadvantageously from 10 to 800 g/ha, preferably from 50 to 300 g/ha forapplications in foliar treatment. The dose of active substance appliedis generally and advantageously from 2 to 200 g per 100 kg of seed,preferably from 3 to 150 g per 100 kg of seed in the case of seedtreatment.

It is clearly understood that the doses indicated herein are given asillustrative examples of the method according to the invention. A personskilled in the art will know how to adapt the application doses, notablyaccording to the nature of the plant or crop to be treated.

The fungicide or insecticide composition according to the invention mayalso be used in the treatment of genetically modified organisms with thecompounds according to the invention or the agrochemical compositionsaccording to the invention. Genetically modified plants are plants intogenome of which a heterologous gene encoding a protein of interest hasbeen stably integrated. The expression “heterologous gene encoding aprotein of interest” essentially means genes which give the transformedplant new agronomic properties, or genes for improving the agronomicquality of the modified plant.

The compounds or mixtures according to the invention may also be usedfor the preparation of composition useful to curatively or preventivelytreat human or animal fungal diseases such as, for example, mycoses,dermatoses, trichophyton diseases and candidiases or diseases caused byAspergillus spp., for example Aspergillus fumigatus.

The various aspects of the invention will now be illustrated withreference to the following tables of compounds and examples. Thefollowing tables illustrate in a non-limiting manner examples ofcompounds according to the invention.

In the following examples, M+1 (or M−1) means the molecular ion peak,plus or minus 1 a.m.u. (atomic mass unit) respectively, as observed inmass spectroscopy and M (Apcl+) means the molecular ion peak as it wasfound via positive atmospheric pressure chemical ionisation in massspectroscopy.

In the following examples, the logP values were determined in accordancewith EEC Directive 79/831 Annex V.A8 by HPLC (High Performance LiquidChromatography) on a reversed-phase column (C 18), using the methoddescribed below:

Temperature: 40° C.; Mobile phases: 0.1% aqueous formic acid andacetonitrile; linear gradient from 10% acetonitrile to 90% acetonitrile.

Calibration was carried out using unbranched alkan-2-ones (comprising 3to 16 carbon atoms) with known logP values (determination of the logPvalues by the retention times using linear interpolation between twosuccessive alkanones).

The lambda max values were determined in the maxima of thechromatographic signals using the UV spectra from 190 nm to 400 nm.

The following examples illustrate in a non-limiting manner thepreparation and efficacy of the compounds of formula (I) according tothe invention.

PREPARATION EXAMPLE 1N′-{2,5-dimethyl-4-[2-(methyl-phenyl-amino)-pyrimidin-4-yloxy]-phenyl}-N-ethyl-N-methyl-formamidine-process(d2)-compound (V) to compound (I)

To a mixture of 252 mg (0.7 mmol) of[4-(4-Amino-2,5-dimethyl-phenoxy)-pyrimidin-2-yl]-methyl-phenyl-amineand 4 ml of trimethoxymethane, 20 mg of p-toluene sulfonic acid wereadded. The reaction mixture was refluxed for 2 hrs and concentrated invacuo. The mixture was solved in 10 ml of dichloromethane and 62 mg(1.05 mmol) methyl ethyl amine was added. After stirring 18 hrs atambient temperature the mixture was evaporated and yielded 280 mg (89%)with a purity of 87%; log P (pH 2.3)=1.61.

Preparation of Starting Material:4-(2-chloro-pyrimidin-4-yloxy)-2.5-dimethyl-phenylamine-process(c)-compound (VI) to compound (V)

A solution of 7.55 g (55 mmol) 4-amino-2,5-dimethylphenol and 2.4 g NaOH(2M) in 30 ml water were added dropwise to a solution of 7.45 g (50.0mmol) of 2,4-dichloropyrimidine in 50 ml of acetone. The reactionmixture was stirred for 20 h at ambient temperature. After concentrationin vacuo and addition of 150 ml water the formed precipitate wasfiltered by suction. Yield 10.6 g (75%) with a purity of 88% log P(pH=2.3)=1.37.

[4-(4-Amino-2,5-dimethyl-phenoxy)-pyrimidin-2-yl]-methyl-phenyl-amine-compound(V)

A solution of 2.50 g (10 mmol)4-(2-chloro-pyrimidin-4-yloxy)-2,5-dimethyl-phenylamine and 2.14 gN-methylaniline (20 mmol) in 50 ml hydrochloric acid were stirred for 20h at 80° C. After cooling down to ambient temperature 50 ml ethylacetate was added and the organic layer was separated. The water layerwas brought to pH 8 with sodium carbonate and the formed precipitate wasfiltered by suction and washed with hexane. After separation the organiclayer was concentrated in vacuo and column chromatography(dichloromethane) yielded 380 mg (11%) with a purity of 89% log P(pH=2.3)=1.72.

PREPARATION EXAMPLE 2N′-{4-[2-(3-chloro-2-methyl-phenoxy)-pyrimidin-4-yloxy]-2,5-dimethyl-phenyl}-N-ethyl-N-methyl-formamidine-process(d1)-compound (V) to compound (I)

To a mixture of 293 mg (0.7 mmol) of4-[2-(3-chloro-2-methyl-phenoxy)-pyrimidin-4-yloxy]-2,5-dimethyl-phenylaminein 20 ml methanol 182 mg (1.05 mmol) ofN-(dimethoxymethyl)-N-methyl-ethanamine (77% pure) was added. Thereaction mixture was stirred for 20 hrs at 45° C. The reaction mixturewas dried over magnesium sulfate concentrated in vacuo and yielded 290mg (76%) with a purity of 78%; log P (pH 2.3)=2.08.

Preparation of Starting Material:4-[2-(3-chloro-2-methyl-phenoxy)-pyrimidin-4-yloxy]-2,5-dimethyl-phenylamine-compound(V)

A solution of 1.43 g (10 mmol) 3-chloro-2-methyl-phenol and 0.4 g sodiumhydride (60% in paraffine, 10 mmol) in 20 ml THF were stirred for 30 minat ambient temperature. After adding 1.25 g (5 mmol)4-(2-chloro-pyrimidin-4-yloxy)-2,5-dimethyl-phenylamine the mixture wasstirred for 20 hrs at 60° C. After cooling down to ambient temperature20 ml water was added and the organic layer was separated, dried overmagnesium sulfate, concentrated in vacuo, column chromatography(cycclhexane/ethyl acetate, 2:1) and a second column chromatography(dichloromethane) yielded 640 mg (30%) with a purity of 85%; log P(pH=2.3)=2.81.

4-(2-chloro-pyrimidin-4-yloxy)-2,5-dimethyl-phenylamine is preparedaccording to preparation example 1.

PREPARATION EXAMPLE 3N′-{4-[(2-chloro-6-methylpyrimidin-4-yl)oxy]-2,5-dimethylphenyl}-N-ethyl-N-methylimido-formamide-process(d1)-compound (V) to compound (I)

To a mixture of 310 mg (0.8 mmol) of4-[(2-chloro-6-methylpyrimidin-4-yl)oxy]-2,5-dimethyl-aniline in 20 mlacetonitrile 208 mg (1.5 mmol) of N-(dimethoxymethyl)-N-methylethanamine(77% pure) was added. The reaction mixture was refluxed for 20 hrs. Thereaction mixture was concentrated in vacuo, diluted with ethyl acetateand washed with water. The organic layer was dried over magnesiumsulfate and concentrated in vacuo yielded 220 mg (59%) with a purity of72% log P (pH=2.3)=1.45.

Preparation of Starting Material:4-(2-chloro-pyrimidin-4-yloxy)-2,5-dimethyl-phenylamine-process(c)-compound (VI) to compound (V)4-[(2-chloro-6-methylpyrimidin-4-yl)oxy]-2,5-dimethylaniline

A solution of 4.53 g (33 mmol) 4-amino-2,5-dimethylphenol and 1.44 gNaOH (2M) in 30 ml water were added dropwise to a solution of 4.89 g(30.0 mmol) of 2,4-dichloropyrimidine in 50 ml of acetone. The reactionmixture was stirred for 20 h at ambient temperature.

After concentration in vacuo and addition of 250 ml water the mixturewas extracted with ethyl acetate. The organic layer was dried overmagnesium sulfate and concentrated in vacuo yielded 5.10 g (52%) with apurity of 81%; log P (pH=2.3)=1.62.

PREPARATION EXAMPLE 89N′-[4-({5-chloro-4-[ethyl(methyl)amino]pyrimidin-2-yl}oxy)-2,5-dimethyl-phenyl]-N-ethyl-N-methylimidoformamide-process(d2)-compound (V) to compound (I)

To a mixture of 320 mg (1.0 mmol) of2-(4-amino-2,5-dimethylphenoxy)-5-chloro-N-ethyl-N-methylpyrimidin-4-amineand 4 ml of trimethoxymethane, 20 mg of p-toluene sulfonic acid wereadded. The reaction mixture was refluxed for 2 hrs and concentrated invacuo. The mixture was solved in 10 ml of dichloromethane and 89 mg (1.5mmol) methyl ethyl amine was added. After stirring 18 hrs at ambienttemperature the mixture was evaporated and yielded 310 (78 with a purityof 95 log P (pH 2.3)=1.82.

Preparation of Starting Material:2-(4-amino-2,5-dimethylphenoxy)-5-chloro-N-ethyl-N-methylpyrimidin-4-amine-process(b)-compound (IV) to compound (V)

To a solution of 8.86 g (20 mmol)5-chloro-2-(2,5-dimethyl-4-nitrophenoxy)-N-ethyl-N-methylpyrimidin-4-aminein 50 ml hydrochloric acid and 50 ml methanol 13.5 g (60 mmol)tin-(II)-dichloro dihydrate was added and the mixture was refluxed for 4h. After cooling down to ambient temperature the formed precipitate wasfiltered by suction, solved in water and brought to pH 8 with aqueoussolution of sodium hydroxide. Ethyl acetate was added and the organiclayer was separated, dried over magnesium sulfate, concentrated in vacuoand column chromatography (cyclohexane/ethyl acetate, 1:1) yielded 4.6 g(72%) with a purity of 96% log P (pH=2.3)=1.88.

5-chloro-2-(2,5-dimethyl-4-nitrophenoxy)-N-ethyl-N-methylpyrimidin-4-amine-process(a)-compound (II) to compound (IV)

A solution of 16.8 g (40 mmol)2,5-dichloro-N-ethyl-N-methylpyrimidin-4-amine, 7.35 g4-nitro-2,5-dimethylphenol (44 mmol) and 8.29 g potassium carbonate (60mmol) in 70 ml DMF were stirred for 20 hrs at 100° C. After adding themixture to 150 ml water the resulting suspension was extracted twicewith 50 ml dichloromethane. The combined organic layers were washed withaqueous solution of sodium hydroxide. The organic layer was dried overmagnesium sulfate, concentrated in vacuo and column chromatography(dichloromethane) yielded 8.3 g (47%) with a purity of 76%; log P(pH=2.3)=4.07.

4-Amino substituted chloro pyrimidines can be prepared by known methods,for example described in Polish Journal of Chemistry (1980), 54(7-8),1557-62.

TABLE 1

N° R¹ R² R³ R⁴ R⁵ R⁶ logP_(a) 1 H Et Me Me Me 2-NMePh 1.61 2 H Et Me MeMe 2-O-(2-methyl-3-chloro-phenyl) 2.08 3 H Et Me Me Me 2-Cl; 4-Me 1.45 4H Et Me Me Me 4-tBu 1.98^(a) 5 H Et Me Me Me4-O-(3-trifluormethyl-phenyl) 4.35^(a) 6 H Et Me Me Me4-(3-trifluormethyl-phenyl) 3.19^(a) 7 H Et Me Me Me 4-CF₃ 1.85^(a) 8 HEt Me Me Me 4-O-(2-methyl-3-chloro-phenyl); 2.6 5-Me 9 H Et Me Me Me4-O-(3-tBu-phenyl) 4.9^(a) 10 H Et Me Me Me 2-NMeEt 0.82 11 H Et Me MeMe 2-OMe 1.16 12 H Pr Me Me Me 2-OMe 1.38 13 H Et Me Me Me 2-NMePr 1.2514 H Et Me Me Me 2-N-imidazolinyl 0.82 15 H Et Me Me Me 4-Cl 1.4 16 H PrMe Me Me 4-Cl 1.56 17 H iPr Me Me Me 4-Cl 1.54 18 H Pr Me Me Me2-O-(2-methyl-3-chloro-phenyl) 2.21 19 H Et Me Me Me 2-N-morpholino 1.320 H Pr Me Me Me 2-N-morpholino 3.13 21 H Et Me Me Me 2-N-piperidino 1.422 H Pr Me Me Me 2-N-piperidino 1.58 23 H Et Me Me Me 2-Cl 1.3 24 H PrMe Me Me 2-Cl 1.44 25 H iPr Me Me Me 2-Cl 1.4 26 H iPr Me Me Me 2-OMe1.4 27 H Et Me Me Me 2-Cl; 5-Me 1.42 28 H Pr Me Me Me 2-Cl; 5-Me 1.68 29H iPr Me Me Me 2-N-(3-chlorophenyl) 2.04 30 H Et Me Me Me2-N-(3-chlorophenyl) 1.94 31 H iPr Me Me Me 2-N-imidazolinyl 1.01 32 HPr Me Me Me 2-Cl; 4-Me 1.62 33 H iPr Me Me Me 2-N-morpholino 1.46 34 HiPr Me Me Me 2-N-piperidino 1.56 35 H Et Me Me Me 2-OPh 1.68 36 H Pr MeMe Me 2-OPh 1.87 37 H Et Me Me Me 2-NMe₂ 0.66 38 H Pr Me Me Me 2-NMe₂0.89 39 H Et Me Me Me 4-OMe 1.32 40 H Pr Me Me Me 4-OMe 1.47 41 H iPr MeMe Me 2-Cl; 4-Me 1.57 42 H Pr Me Me Me 4-NMeEt 1.6 43 H Et Me Me Me4-NMeEt 1.46 44 H iPr Me Me Me 2-OEt 1.62 45 H iPr Me Me Me 4-NMeEt 1.5646 H iPr Me Me Me 2-Cl; 5-Me 1.62 47 H Et Me Me Me 2-OEt 1.47 48 H iPrMe Me Me 4-OMe 1.49 49 H Et Me Me Me 4-NMePr 1.74 50 H Pr Me Me Me 2-OEt1.55 51 H Pr Me Me Me 4-NMePr 1.79 52 H Pr Me Me Me 2-N-(3-chlorophenyl)2.06 53 H iPr Me Me Me 4-NMePr 1.77 54 H —(CH₂)₅— Me Me 2-NEt 0.98 55 HEt Me Me Me 2-NEt 0.72 56 H —(CH₂)₅— Me Me 2-NPr 1.13 57 H Et Me Me Me2-NPr 0.97 58 H Et Me Me Me 2-NMe 0.44 59 H Et Me Me Me 2-tBu; 4-Cl 2.6160 H iPr Me Me Me 2-tBu; 4-Cl 2.8 61 H —(CH₂)₅— Me Me 2-NMePh 1.84 62 H—(CH₂)₅— Me Me 2-NMe 0.87 63 H Me Me Me Me 2-PhO 1.65 64 H Et Me Me Me2,5-Cl₂ 1.67 65 H Et Me Me Me 2-(3-Cl-PhO) 2.04 66 H iPr Me Me Me 2-PhO1.81 67 H Pr Me Me Me 2-(3-Cl-PhO) 2.14 68 H iPr Me Me Me 2-(3-Cl-PhO)2.12 69 H Et Me Me Me 2,4-Cl₂ 1.67 70 H Et Me Me Me 2-(3,4-F₂-PhO) 1.9371 H Et Me Me Me 2-(3,4-MeO-PhO) 1.65 72 H Et Me Me Me 2-PhO 1.96 73 HEt Me Me Me 2-PhO-4-Me 1.99 74 H —(CH₂)₅— Me Me 2-(3,4-MeO-PhO) 1.80 75H —(CH₂)₅— Me Me 2-PhO-4-Me 2.09 76 H —(CH₂)₅— Me Me 2-PhO 2.02 77 H EtMe Me Me 2-(4-tBu-PhO) 2.65 78 H —(CH₂)₅— Me Me 2-(4-tBu-PhO) 2.75 79 HEt Me Me Me 2-(3-Me-PhO) 2.02 80 H —(CH₂)₅— Me Me 2-(3-Me-PhO) 2.16 81 HEt Me Me Me 2-(4-Cl-PhO) 2.11 82 H —(CH₂)₅— Me Me 2-(4-Cl-PhO) 2.18 83 HEt Me Me Me 4-Et; 5-Cl 1.91 84 H Pr Me Me Me 4-Et; 5-Cl 1.99 85 H—(CH₂)₅— Me Me 4-Et; 5-Cl 1.98 86 H —(CH₂)₄— Me Me 4-Et; 5-Cl 1.87 87 HEt Me Me Me 2-(4-CF₃-PhO) 2.37 88 H —(CH₂)₅— Me Me 2-(4-CF₃-PhO) 2.49^(a)logP_(a) measured at pH = 4

TABLE 2

N° R¹ R² R³ R⁴ R⁵ R⁶ logP_(a) 89 H Et Me Me Me 2-NMeEt; 3-Cl 1.82 90 HEt Me Me Me 2-CF₃ 0.22^(a) 91 H Et Me H H 2-CF₃; 4-iPr 367^(b) 92 H EtMe Me iPr 2-CF₃ 1.10^(a) 93 H Et Me Me Me 2-Me; 3-Me 1.19 94 H Pr Me MeMe 2-Me; 3-Me 1.4 95 H Et Me Me Me 3-Cl 1.32 96 H Pr Me Me Me 3-Cl 1.4897 H iPr Me Me Me 3-Cl 1.41 98 H Pr Me Me Me 2-CF₃ 1.7 99 H iPr Me Me Me2-NMeEt; 3-Cl 1.98 100 H Pr Me Me Me 2-NMeEt; 3-Cl 1.95 101 H —(CH₂)₅—Me Me 2-NMeEt; 3-Cl 1.93 102 H Et Me Me Me 2-PhO 1.82 103 H Et Me Me Me2-(3-Cl-PhO) 2.13 ^(a)logP_(a) measured at pH = 4 ^(b)(M + 1)—massspectroscopy measured

EFFICACY EXAMPLE A In Vivo Preventive Test on Puccinia recondita f. Sp.tritici (Wheat Brown Rust)

Solvent: 50 parts by weight of N,N-dimethylacetamide Emulsifier: 1 partby weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvent andemulsifier, and the concentrate is diluted with water to the desiredconcentration.

To test for preventive activity, young plants are inoculated with aspore suspension of Puccinia recondita in a 0.1% strength aqueous agarsolution. After the spray coating has dried on, the plants are sprayedwith the preparation of active compound at the stated rate ofapplication. The plants remain for 24 hours in an incubation cabinet at20° C. and a relative atmospheric humidity of 100%.

The plants are placed in a greenhouse at a temperature of approximately20° C. and a relative atmospheric humidity of approximately 80% topromote the development of rust pustules.

The test is evaluated 10 days after the inoculation. 0% means anefficacy which corresponds to that of the control, while an efficacy of100% means that no disease is observed.

In this test the following compounds according to the invention showedan efficacy of 70% or even higher at a concentration of 1000 ppm ofactive ingredient: 1, 2, 3, 10, 11, 13, 15, 18, 19, 21, 22, 23, 26, 30,31, 32, 33, 34, 37, 38, 39, 41, 43, 46, 47, 49, 52, 53, 54, 55, 56, 57,58, 62, 64, 65, 66, 67, 68, 69, 70, 71, 73, 74, 76, 77, 78, 79, 80, 81,82, 83, 87, 88, 89, 99, 101.

EFFICACY EXAMPLE B In Vivo Preventive Test on Erysiphe gramini (PowderyMildew on Barley)

Solvent: 50 parts by weight of N,N-dimethylacetamide Emulsifier: 1 partby weight of alkylaryl polyglycol ether

To produce a suitable preparation of active compound, 1 part by weightof active compound or active compound combination is mixed with thestated amounts of solvent and emulsifier, and the concentrate is dilutedwith water to the desired concentration.

To test for preventive activity, young plants are sprayed with thepreparation of active compound or active compound combination at thestated rate of application.

After the spray coating has dried on, the plants are dusted with sporesof Erysiphe graminis f. sp. hordei.

The plants are placed in a greenhouse at a temperature of approximately20° C. and a relative atmospheric humidity of approximately 80% topromote the development of mildew pustules.

The test is evaluated 7 days after the inoculation. 0% means an efficacywhich corresponds to that of the control, while an efficacy of 100%means that no disease is observed.

In this test the following compounds according to the invention showedan efficacy of 70% or even higher at a concentration of 1000 ppm ofactive ingredient: 1, 2, 3, 5, 7, 8, 10, 11, 13, 15, 18, 19, 21, 23, 30,32, 33, 37, 38, 41, 47, 49, 55, 58, 59, 60, 61, 89, 90, 101.

EFFICACY EXAMPLE C In Vivo Protective Test on Alternaria solani (LeafSpot of Tomato)

Solvent: 49 parts by weight of N,N-dimethylformamide Emulsifier: 1 partby weight of alkylarylpolyglycolether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvent andemulsifier, and the concentrate is diluted with water to the desiredconcentration.

To test for protective activity, young plants are sprayed with thepreparation of active compound at the stated rate of application. Afterthe spray coating has dried on, the plants are inoculated with anaqueous spore suspension of Alternaria solani. The plants remain for oneday in an incubation cabinet at approximately 20° C. and a relativeatmospheric humidity of 100%. Then the plants are placed in anincubation cabinet at approximately 20° C. and a relative atmospherichumidity of 96%.

The test is evaluated 7 days after the inoculation. 0% means an efficacywhich corresponds to that of the control while an efficacy of 100% meansthat no disease is observed.

In this test, invention related compounds of the following formularevealed an efficacy of 70% or higher at a concentration of 500 ppm ofactive ingredient: 1, 4, 10.

EFFICACY EXAMPLE D In Vivo Protectice Test on Podosphaera leucotricha(Apples)

Solvent: 24.5 parts by weight of acetone 24.5 parts by weight ofdimethylacetamide Emulsifier: 1 part by weight of alkylaryl polyglycolether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvent andemulsifier, and the concentrate is diluted with water to the desiredconcentration.

To test for protective activity, young plants are sprayed with thepreparation of active compound at the stated rate of application. Afterthe spray coating has dried on, the plants are inoculated with anaqueous spore suspension of the causal agent of apple mildew(Podosphaera leucotricha). The plants are then placed in a greenhouse atapproximately 23° C. and a relative atmospheric humidity ofapproximately 70%.

The test is evaluated 10 days after the inoculation. 0% means anefficacy which corresponds to that of the control, while an efficacy of100% means that no disease is observed.

In this test the compounds according to the invention of the followingstructures showed efficacy of 70% or even higher at a concentration of100 ppm of active ingredient: 1, 4, 5, 7, 10, 13, 35, 61, 81, 82, 87,88, 92.

EFFICACY EXAMPLE E In Vivo Protective Test on Sphaerotheca fuliginea(Cucumbers)

Solvent: 24.5 parts by weight of acetone 24.5 parts by weight ofdimethylacetamide Emulsifier: 1 part by weight of alkylaryl polyglycolether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvent andemulsifier, and the concentrate is diluted with water to the desiredconcentration.

To test for protect activity, young plants are sprayed with thepreparation of active compound at the stated rate of application. Afterthe spray coating has dried on, the plants are inoculated with anaqueous spore suspension of Sphaerotheca fuliginea. The plants are thenplaced in a greenhouse at approximately 23° C. and a relativeatmospheric humidity of approximately 70%.

The test is evaluated 7 days after the inoculation. 0% means an efficacywhich corresponds to that of the control, while an efficacy of 100%means that no disease is observed.

In this test the compounds according to the invention of the followingstructures showed efficacy of 70% or even higher at a concentration of100 ppm of active ingredient: 1, 2, 4, 5, 6, 7, 8, 10, 13, 30, 41, 47,59, 60, 61, 67, 70, 78, 79, 81, 82, 87, 88, 92.

EFFICACY EXAMPLE F In Vivo Protective Test on Uromyces appendiculatus(Beans)

Solvent: 24.5 parts by weight of acetone 24.5 parts by weight ofdimethylacetamide Emulsifier: 1 part by weight of alkylaryl polyglycolether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amounts of solvent andemulsifier, and the concentrate is diluted with water to the desiredconcentration.

To test for protective activity, young plants are sprayed with thepreparation of active compound at the stated rate of application. Afterthe spray coating has dried on, the plants are inoculated with anaqueous spore suspension of the causal agent of bean rust (Uromycesappendiculatus) and then remain for 1 day in an incubation cabinet atapproximately 20° C. and a relative atmospheric humidity of 100%.

The plants are then placed in a greenhouse at approximately 21° C. and arelative atmospheric humidity of approximately 90%.

The test is evaluated 10 days after the inoculation. 0% means anefficacy which corresponds to that of the control, while an efficacy of100% means that no disease is observed.

In this test the compounds according to the invention of the followingstructures showed efficacy of 70% or even higher at a concentration of100 ppm of active ingredient: 41, 47, 49, 59, 60, 70, 81, 82, 87, 88.

EFFICACY EXAMPLE G In Vivo Protective Test on Myzus persicae (MYZUPE)

Solvent:  78 parts by weight acetone 1.5 parts by weightdimethylformamide Dye: 0.5 parts by weight alkylarylpolyglcolether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amount of solvent andemulsifier, and the concentrate is diluted with emulsifier-containingwater to the desired concentration.

Chinese cabbage (Brassica pekinesis) leaf-disks infected with allinstars of the green peach aphid (Myzus persicae), are sprayed with apreparation of the active ingredient at the desired concentration.

After the specified period of time, mortality in % is determined. 100%means that all aphids have been killed; 0% means that none of the aphidshave been killed.

In this test for example, the following compounds from the preparationexamples showed good activity: 36, 41, 65.

EFFICACY EXAMPLE H In Vivo Protective Test on Phaedon cochleariae(PHAECO)

Solvent:  78 parts by weight of acetone  1.5 parts by weight ofdimethylformamide Dye: 0.5 parts by weight of alkylaryl polyglycolether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amount of solvent andemulsifier, and the concentrate is diluted with emulsifier-containingwater to the desired concentration.

Chinese cabbage (Brassica pekinesis) leaf-disks are sprayed with apreparation of the active ingredient of the desired concentration. Oncedry, the leaf disks are infested with mustard beetle larvae (Phaedoncochleariae).

After the specified period of time, mortality in % is determined. 100%means that all beetle larvae have been killed and 0% means that none ofthe beetle larvae have been killed.

In this test, for example, the following compounds from the preparationexamples showed good activity: 18.

EFFICACY EXAMPLE I In Vivo Protective Test on Tetranychus urticae(TETRUR)

Solvent:  78 parts by weight acetone 1.5 parts by weightdimethylformamide Dye: 0.5 parts by weight alkylarylpolyglcolether

To produce a suitable preparation of active compound, 1 part by weightof active compound is mixed with the stated amount of solvent andemulsifier, and the concentrate is diluted with emulsifier-containingwater to the desired concentration.

French bean (Phaseolus vulgaris) which are heavily infested with allstages of the two spotted spidermite (Tetranychus urticae), are sprayedwith a preparation of the active ingredient at the desiredconcentration.

After the specified period of time, mortality in % is determined. 100%means that all spider mites have been killed and 0% means that none ofthe spider mites have been killed.

In this test, for example, the following compounds from the preparationexamples showed good activity: 37.

1. A phenyl-amidine derivative of formula (I):

wherein R¹ represents H, a substituted or non substituted C₁-C₁₂-alkyl,a substituted or non substituted C₂-C₁₂-alkenyl, a substituted or nonsubstituted C₂-C₁₂-alkynyl, SH or a substituted or non substitutedS—C₁-C₁₂-alkyl; R² represents a substituted or non substitutedC₁-C₁₂-alkyl; R³ represents a substituted or non substitutedC₂-C₁₂-alkyl, substituted or non substituted C₃-C₆-cycloalkyl,substituted or non substituted C₂-C₁₂-alkenyl, substituted or nonsubstituted C₂-C₁₂-alkynyl, halogeno-C₁-C₁₂-alkyl; or R¹ and R², R¹ andR³ or R² and R³ can form together a substituted or non substituted 5 to7-membered heterocycle; R⁴ represents a substituted or non substitutedC₁-C₁₂-alkyl, a halogen atom, halogeno-C₁-C₁₂-alkyl, substituted or nonsubstituted O—C₁-C₁₂-alkyl or cyano; R⁵ represents H, a substituted ornon substituted C₁-C₁₂-alkyl, a halogen atom, halogeno-C₁-C₁₂-alkyl,substituted or non substituted O—C₁-C₁₂-alkyl or cyano; R⁶ represents H,halogen, CN, substituted or non substituted phenoxy, substituted or nonsubstituted C₁-C₁₂-alkyl, halogeno-C₁-C₁₂-alkyl, OR⁷, SR⁷,trialkyl-silyl, COOR⁷, C(R⁷)═NOR⁷; NR⁷R⁸; R⁷, R⁸ represent independentlyH, substituted or non substituted C₁-C₁₂-alkyl, aryl or R⁷ and R⁸ canform a substituted or non substituted, saturated or non saturated 5 to7-membered heterocycle including one or more atoms selected in the listconsisting of O, N and S; m represents 1, 2 or 3; as well as a salt,N-oxyde, metallic complex, metalloidic complex and/or an opticallyactive isomer thereof.
 2. A compound of formula (I) according to claim 1wherein R¹ represents H, C₁-C₁₂-alkyl or SH; or R² represents methyl; orR³ represents C₂-C₁₂-alkyl, C₂-C₁₂-alkenyl, C₃-C₆-cycloalkyl; or R² andR³ can form together a substituted or non substituted 5- to 7-memberedheterocycle; or R⁴ represents C₁-C₁₂-alkyl or a halogen atom; or R⁵H, asubstituted or non substituted C₁-C₆-alkyl, a halogen atom,halogeno-C₁-C₆-alkyl, substituted or non substituted O—C₁-C₆-alkyl orCN; or R⁶ which may be the same or different, represents H, halogen, CN,substituted or non substituted phenoxy, substituted or non substitutedC₁-C₁₂-alkyl, halogeno-C₁-C₁₂-alkyl, OR⁷, SR⁷, trialkyl-silyl, COOR⁷,C(R⁷)═NOR⁷; NR⁷R⁸.
 3. A compound of formula (I) according to claim 1wherein R¹ represents C₁-C₁₂-alkyl; or R³ represents a non substitutedC₂-C₄-alkyl, C₃-C₄-alkenyl or cyclopropyl; or R² and R³ can formtogether a 6-membered heterocycle; or R⁴ represents a non substitutedC₁-C₁₂-alkyl or a chlorine atom; or R⁶ represents a branchedC₁-C₁₂-alkyl.
 4. A compound of formula (I) according to claim 1 whereinR¹ represents methyl; or R³ represents ethyl, n-propyl, i-propyl,propenyl or allyl; or R² and R³ can form together a pipiridinyl or apyrrolidinyl; or R⁴ represents methyl.
 5. A compound of formula (I)according to claim 1 wherein R² and R³ form together abis-alkylated-pyrrolidinyl.
 6. A compound of formula (I) according toclaim 5 wherein R² and R³ form together a bis-methyl-pyrrolidinyl.
 7. Aprocess for the preparation of a compound of formula (I) according toclaim 1 comprising at least one of the following steps:


8. A method for controlling phytopathogenic fungi of crops, comprisingapplying an agronomically effective and substantially non-phytotoxicquantity of a compound according to claim 1 to soil where a plant growor is capable of growing, to the leaves or fruit of a plant and/or to aseed of a plant.
 9. A method for controlling damaging insects comprisingapplying a compound of formula (I) according to claim 1 to a seed, aplant and/or to a fruit of a plant and/or to soil wherein a plant isgrowing or wherein a plant is desired to grow.